1. Field of the Invention
The present invention relates to body-treating compositions and methods, and more particularly, to an injectable, mechanically sheared collagen fiber implant material, and methods of preparing and using same.
2. Background
Collagen has been used as an implant material to replace or augment hard or soft connective tissue, such as skin, tendons, cartilage, bone and interstitium. Early collagen implants were often solid collagen masses which were crosslinked with chemical agents, radiation or other means to improve mechanical properties, decrease immunogenicity and/or increase resistance to resorption. A major disadvantage of solid crosslinked collagen implants is the requirement for surgical implantation by means of incision. Lack of deformability and flexibility are other disadvantages of solid collagen implants.
An effective alternative to surgically implanted solid collagen material is disclosed in U.S. Pat. No. 3,949,073, and involves the use of an atelopeptide solution of collagen as an injectable implant material for augmenting soft tissue. The implant material is prepared first by forming a solution of atelopeptide collagen fibers, typically by treating a collagen source with one of more proteolytic enzymes which are active at low pH. The solubilized fibers have the ability to form a reconstituted fibrous mass as the pH, ionic strength and/or temperature of the fiber solution is raised. In practicing the method of the '073 patent, a solubilized fiber suspension is brought to physiological ionic strength and pH conditions, and injected by means of a hypodermic needle into the site to be augmented. The fiber reconstitution process, which begins before injection, and continues at the augmentation site, produces a fibrous collagen mass which has a number of important advantages over solid collagen implants, in addition to the advantages of injectability.
Commonly owned U.S. Pat. No. 4,424,208 describes an injectable collagen material containing both reconstituted collagen and chemically crosslinked atelopeptide collagen. This material provides improved persistence, i.e., implant volume constancy, over the reconstituted, non-crosslinked implant material reported in the above '073 patent.
Despite the advantages and overall usefulness of the injectable collagen implant materials disclosed in the above-cited patents, problems associated with injecting the materials have been encountered, particularly where the materials have been stored over extended periods. One problem is relatively high extrusion forces--greater than about 50-60N (newtons)--which may be required to force the collagen material through a suitable-sized hypodermic needle. A related problem is the tendency of the material to form local obstructions in the needle, causing a "spiking" effect characterized by sharp increases in the pressure needed to force material through the needle. In an extreme case, the needle or syringe can become blocked with aggregated collagen fibers, causing injectable material to ooze out of the syringe, at the needle connection, with continued pressure application to the syringe. The combined high viscosity, spiking and oozing problems can render the material unsuitable for use in collagen-injection treatment, and to the extent these problems increase over storage time, can limit the effective shelf-life of the implant material.
An improved crosslinked collagen implant material which has a reduced viscosity has been disclosed in co-owned, continuation-in-part U.S. patent application for "Injectable Cross-Linked Collagen Implant Material", Ser. No. 663,478, filed Oct. 28, 1984, now U.S. Pat. No. 4,582,640. The improved material is prepared by crosslinking reconstituted atelopeptide collagen under conditions which lead predominantly to intrafibrillar crosslinks. In addition to lowered viscosity, the crosslinked material also shows improved persistence and resistance to proteolytic degradation relative to the two patented materials described above. Despite these advantages, problems relating to spiking and syringe blockage has been encountered in administering the material by injection, particularly after storage periods of several months.